凋亡抑制蛋白对大鼠心肌缺血再灌注损伤的影响
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摘要
目的
通过建立大鼠心肌缺血再灌注(IR)模型,观察凋亡抑制蛋白(IAP)Livin过表达对大鼠心肌缺血再灌注损伤(IRI)的影响,探讨IRI的发生机制和防治方法。
方法
健康SD大鼠69只,随机分为缺血再灌注组(IR组,n=23)、Livin组(简称L组,n=23)和空白对照组(Sham组,简称S组,n=23)。建立大鼠心肌IR模型:IR组及L组缺血45min,再灌注120 min;L组在IR前24h心肌内注射表达Livin(3.9×10~7 cfu/ml)的逆转录病毒载体0.05ml。观察指标:(1)硫磺素S染色法评估心肌无复流区范围(NRA);(2)TTC染色法检测心肌梗死区范围(MIS);(3)生化自动分析仪测定血清CK-MB水平;(4)TUNEL法标记心肌凋亡细胞,统计心肌细胞凋亡指数(AI)。
结果
(1) S组心肌灌注良好,无NR现象发生;IR组NRA为(25.93±6.45),与S组相比显著增加(P＜0.05);L组NRA为(19.39±6.25),与IR组相比显著降低(P＜0.05),但仍显著大于S组(P＜0.05)。(2)S组无心肌梗死;IR组MIS为(28.62±3.43),与S组相比显著增加(P＜0.05);L组MIS为(22.14±2.98),与IR组相比明显缩小(P＜0.05),但仍显著大于S组(P＜0.05)。(3)S组血清CK-MB水平为(10.30±1.49)u/L;IR组血清CK-MB水平为(99.80±3.01),与S组相比显著增高(P＜0.05);L组血清CK-MB水平为(70.90±2.60),与IR组相比明显降低(P＜0.05),但仍显著高于S组(P＜0.05)。(4)S组心肌细胞AI为(1.08±0.32);IR组AI为(11.52±2.58),与S组相比显著增高(P＜0.05);L组心肌细胞AI为(5.05±1.74),与IR组相比明显降低(P＜0.05),但仍显著高于S组(P＜0.05)。
结论
(1)缺血再灌注过程中心肌细胞凋亡增多;
(2) Livin过表达抑制缺血再灌注过程中心肌细胞凋亡,减少缺血再灌注NRA和MIS;
(3) Livin过表达抑制心肌细胞凋亡,在IRI过程中发挥心肌保护作用。
Objective
To explore the mechanisms of ischemia reperfusion injury (IRI) and the effects of Livin over-expression on IRI.
Methods
69 Sprague-Dawley (SD) rats were divided into Sham group, ischemia reperfusion (IR) group and Livin group randomly. Rats in IR and Livin groups were subjected to 45min of left coronary artery occlusion followed by 120min of reperfusion. Rats in Livin group were treated with retrovirus vector expressing Livin protein by intramyocardial injection 24h before left coronary artery occlusion. The no-reflow area (NRA) was evaluated by injection of thioflavine S into the auticle of left atrium,and myocardial infarction size ( MIS ) was evaluated by triphenyltetrazolium (TTC) staining method at the end of reperfusion. Serum level of creatine kinase isozyme (CK-MB) was measured at the end of reperfusion. The myocardial apoptosis was determined with terminal deoxynucleotidyl transferase-mediated dUTP- fluorescein nick end labeling( TUNEL) method .
Results
(1) The myocardial perfusion in Sham group is sufficient,without no reflow phenomenon. No reflow area both in Livin group and in IR group were larger than that of Sham group. Compared with IR group, no-reflow area in Livin group was reduced significantly (19.39±6.25 vs 25.93±6.45,P<0.05). (2) Myocardial infarction size was significantly reduced in Livin group compared with IR group (22.14±2.98 vs 28.62±3.43,P <0.05), but either in Livin group or in IR group was larger than that of Sham group. (3) Serum level of CK-MB both in IR group and in L group were higher than that of Sham group,but Serum level of CK-MB in L group was lower than that of IR group. (4) we examined the presence of apoptosis during ischemia reperfusion, which was significantly higher in IR group and in Livin group compared with Sham group (11.52±2.58 vs 1.08±0.32, P <0.05). Apoptosis rate was significantly reduced after Livin injection (11.52±2.58 vs 5.05±1.74, P <0.05) .
Conclusion
(1) Apoptosis was increased in the process of myocardial ischemia reperfusion.
(2) Livin over-expression can reduce NRA and MIS, inhibit myocardial apoptosis in the process of myocardial ischemia reperfusion.
(3) Apoptosis participated in the process of myocardial ischemia reperfusion injury.By inhibiting myocardial apoptosis, Livin over-expression can protect the heart against ischemia reperfusion injury.
通过建立大鼠心肌缺血再灌注(IR)模型,观察凋亡抑制蛋白(IAP)Livin过表达对大鼠心肌缺血再灌注损伤(IRI)的影响,探讨IRI的发生机制和防治方法。
方法
健康SD大鼠69只,随机分为缺血再灌注组(IR组,n=23)、Livin组(简称L组,n=23)和空白对照组(Sham组,简称S组,n=23)。建立大鼠心肌IR模型:IR组及L组缺血45min,再灌注120 min;L组在IR前24h心肌内注射表达Livin(3.9×10~7 cfu/ml)的逆转录病毒载体0.05ml。观察指标:(1)硫磺素S染色法评估心肌无复流区范围(NRA);(2)TTC染色法检测心肌梗死区范围(MIS);(3)生化自动分析仪测定血清CK-MB水平;(4)TUNEL法标记心肌凋亡细胞,统计心肌细胞凋亡指数(AI)。
结果
(1) S组心肌灌注良好,无NR现象发生;IR组NRA为(25.93±6.45),与S组相比显著增加(P＜0.05);L组NRA为(19.39±6.25),与IR组相比显著降低(P＜0.05),但仍显著大于S组(P＜0.05)。(2)S组无心肌梗死;IR组MIS为(28.62±3.43),与S组相比显著增加(P＜0.05);L组MIS为(22.14±2.98),与IR组相比明显缩小(P＜0.05),但仍显著大于S组(P＜0.05)。(3)S组血清CK-MB水平为(10.30±1.49)u/L;IR组血清CK-MB水平为(99.80±3.01),与S组相比显著增高(P＜0.05);L组血清CK-MB水平为(70.90±2.60),与IR组相比明显降低(P＜0.05),但仍显著高于S组(P＜0.05)。(4)S组心肌细胞AI为(1.08±0.32);IR组AI为(11.52±2.58),与S组相比显著增高(P＜0.05);L组心肌细胞AI为(5.05±1.74),与IR组相比明显降低(P＜0.05),但仍显著高于S组(P＜0.05)。
结论
(1)缺血再灌注过程中心肌细胞凋亡增多;
(2) Livin过表达抑制缺血再灌注过程中心肌细胞凋亡,减少缺血再灌注NRA和MIS;
(3) Livin过表达抑制心肌细胞凋亡,在IRI过程中发挥心肌保护作用。
Objective
To explore the mechanisms of ischemia reperfusion injury (IRI) and the effects of Livin over-expression on IRI.
Methods
69 Sprague-Dawley (SD) rats were divided into Sham group, ischemia reperfusion (IR) group and Livin group randomly. Rats in IR and Livin groups were subjected to 45min of left coronary artery occlusion followed by 120min of reperfusion. Rats in Livin group were treated with retrovirus vector expressing Livin protein by intramyocardial injection 24h before left coronary artery occlusion. The no-reflow area (NRA) was evaluated by injection of thioflavine S into the auticle of left atrium,and myocardial infarction size ( MIS ) was evaluated by triphenyltetrazolium (TTC) staining method at the end of reperfusion. Serum level of creatine kinase isozyme (CK-MB) was measured at the end of reperfusion. The myocardial apoptosis was determined with terminal deoxynucleotidyl transferase-mediated dUTP- fluorescein nick end labeling( TUNEL) method .
Results
(1) The myocardial perfusion in Sham group is sufficient,without no reflow phenomenon. No reflow area both in Livin group and in IR group were larger than that of Sham group. Compared with IR group, no-reflow area in Livin group was reduced significantly (19.39±6.25 vs 25.93±6.45,P<0.05). (2) Myocardial infarction size was significantly reduced in Livin group compared with IR group (22.14±2.98 vs 28.62±3.43,P <0.05), but either in Livin group or in IR group was larger than that of Sham group. (3) Serum level of CK-MB both in IR group and in L group were higher than that of Sham group,but Serum level of CK-MB in L group was lower than that of IR group. (4) we examined the presence of apoptosis during ischemia reperfusion, which was significantly higher in IR group and in Livin group compared with Sham group (11.52±2.58 vs 1.08±0.32, P <0.05). Apoptosis rate was significantly reduced after Livin injection (11.52±2.58 vs 5.05±1.74, P <0.05) .
Conclusion
(1) Apoptosis was increased in the process of myocardial ischemia reperfusion.
(2) Livin over-expression can reduce NRA and MIS, inhibit myocardial apoptosis in the process of myocardial ischemia reperfusion.
(3) Apoptosis participated in the process of myocardial ischemia reperfusion injury.By inhibiting myocardial apoptosis, Livin over-expression can protect the heart against ischemia reperfusion injury.
引文
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